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Abstract
Introduction/Background Clinical symptoms of children with organic, functional, and eosinophilic disease overlap. It is therefore imperative to establish guidance on reference values which numbers of mucosal eosinophils (eos) in the gastrointestinal (GI) tract of children without an organic disease are considered normal. In contrast to eosinophilic oesophagitis, other eosinophilic gastrointestinal diseases (EGIDs) are currently not well defined and evidence-based treatment requires definition of which eosinophil numbers are considered pathological.
Aim To assess the peak number of eosinophils in each segment of the GI tract in ‘’healthy’’ children who have not been diagnosed with an organic disease within at least one year post endoscopy and had either spontaneous resolution of symptoms or were diagnosed with functional GI disorders (FGIDs) as per Rome criteria.
Methods Retrospective study of a tertiary UK paediatric centre, as part of European collaborative project. Patients with macroscopically normal endoscopy and no underlying diagnosis of inflammatory bowel disease, coeliac disease, parasitic infection, or other defined disorders were included. All biopsies were reviewed by a single pathologist and critically reviewed by a second pathologist. The formula: eos/mm²= (eos/HPF) x(1/area of microscope HPF in mm²) was used to standardise the results.
Results We identified 65 patients (males: n=36, 55%) with median age 13.3 (range 1.5 – 16.5) years who underwent endoscopy between January 2017 and December 2018. The commonest reasons for endoscopy were abdominal pain (89%), followed by diarrhoea (58%) and faltering growth (20%), upon referral; a history of atopy was reported for n=6 patients (9%). Majority of patients (n=42, 65%) were diagnosed with a FGID at the last follow up, whereas spontaneous resolution of symptoms was reported in 23 patients (35%). No histological features of eosinophil activation were noted in this cohort, and age was not a discriminatory factor.
Peak eosinophilic concentrations (IQR, eos/hpf, table 1) were: oesophagus 0–0, stomach 0–1, duodenal bulb 8–14, second part of duodenum 3–9, terminal ileum 6–13, caecum 11–23, ascending colon 9–21, transverse colon 5–17, descending colon 5–14, sigmoid 4–12, rectum 1–7; however, numbers were higher in outliers. The peak density of eosinophils, as shown on figure 1, increased progressively from oesophagus to caecum, and then steadily decreased towards the rectum. Importantly, there were no significant differences in eosinophil density between patients with and without FGIDs.
Summary/Conclusions We conducted the first cohort study from the UK illustrating median and peak concentration of eosinophils in each segment of the GI tract in healthy children since Behjati et al described paediatric eosinophilic colitis in 2009. In accordance with our European partners, we recommend a standardised way of reporting eosinophil density (eos/mm²) for use in histological analysis; this allows for objective comparisons to be made and benchmarking between different centres.
The prevalence of EGID for different sections of the GI tract ranges from 3.8–8.5/100,000 and exerts a substantial burden to patients and families. Evidence-based quantitative assessment of eosinophils in the intestine provides a pivotal tool to guide clinicians for rational decision making in differential diagnosis and management of mucosal, functional, and organic diseases of the GI tract.
Peak number of eosinophils in the GI tract
